• Title/Summary/Keyword: IGF-1, IGF-1R

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The Effect of Growth Hormone on mRNA Expression of the GABAB1 Receptor Subunit and GH/IGF Axis Genes in a Mouse Model of Prader-Willi Syndrome

  • Lee, Jin Young;Jin, Dong-Kyu
    • Journal of mucopolysaccharidosis and rare diseases
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    • v.1 no.2
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    • pp.54-59
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    • 2015
  • Purpose: Growth hormone (GH) therapy substantially improves several cognitive functions in PWS. However, the molecular mechanisms underlying the beneficial effects of GH on cognition remain unclear in PWS. In this study, we investigated the effects of recombinant human GH on the gene expression of GABAB receptor subunits and GH/insulin-like growth factor (IGF) axis genes in the brain regions of PWS-mimicking mice (Snord116del). Methods: Snord116del mice were injected subcutaneously with 1.0 mg/kg GH or saline, once daily for 7 days. The collected brain tissues were analyzed for mRNA content using quantitative PCR (qPCR) in the cerebellum, hippocampus, and cerebral cortex. Results: GH increased the mRNA expression level of the $GABA_{B1}$ receptor subunit ($GABA_{BR1}$) and IGF-1R in the cerebellum. Furthermore, a significant positive correlation was found between the level of $GABA_{BR1}$ mRNA and the expression of the IGF-1R transcript. GH also induced an increase in the mRNA expression of IGF-2 and IGF-2R in the cerebellum. Conclusion: These data indicate that GH may provide beneficial effects on cognitive function through its influences on the expression of $GABA_{BR1}$ and GH/IGF-1 axis genes in PWS patients.

Insulin-Like Growth Factors-1 Receptor (IGF-1R) Expression and the Phosphorylation of Endogenous Substrates Lead to Maturation of the Pacific oyster, Crassostrea gigas

  • Park, Su-Jin;Choi, Youn Hee
    • Development and Reproduction
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    • v.25 no.1
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    • pp.67-72
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    • 2021
  • This study investigated the IGF-1 signal in specific tissues using Pacific oysters artificially matured via water temperature elevation. Pacific oysters were subjected to water temperature elevation from March to June, and 20 were randomly sampled each month. The condition index (CI) and tissue weight rate (TWR) were examined by measuring shell length, shell height, shell width, and soft tissue weight. The IGF-1 signal in tissues (adductor muscle, digestive glands, gills, labial palps, mantle edges, and gonads) was analyzed by sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting. From April to June, the TWR of females and males increased from 19.1±2.9 to 21.0±3.6 and 18.2±2.0 to 19.2±2.5, respectively, while the CI remained the same. The IGF-1 signal in each tissue differed. IGF-1 was expressed in the adductor muscle, while tyrosine was expressed in all tissues. The phosphor (p)-ERK and p-AKT activities were high in the adductor muscle, mantle edge, and gonads. IGF-1 signaling affected the growth and maturity of the Pacific oysters examined.

The Relationships between Plasma Insulin-like Growth Factor (IGF)-1 and IGF-Binding Proteins (IGFBPs) to Growth Pattern, and Characteristics of Plasma IGFBPs in Steers

  • Lee, H.G.;Hidari, H.;Kang, S.K.;Hong, Z.S.;Xu, C.X.;Kim, S.H.;Seo, K.S.;Yoon, D.H.;Choi, Y.J.
    • Asian-Australasian Journal of Animal Sciences
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    • v.18 no.11
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    • pp.1575-1581
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    • 2005
  • This study was conducted to determine the characteristics of IGFBPs in plasma of steers, and to profile the relationship between growth and plasma IGF-1 and IGFBPs with aging in Holstein steers. Four blots of IGFBP at molecular weights of 38-43, 34, 29-32 and 24 kDa bands were detected by western ligand blot assay using $^{125}I-IGF-1$. On the basis of immunoblotting with anti-bovine IGFBP-2 and -3 antiserums, we observed the band for IGFBP-2 at approximately 34 kDa, and the IGFBP-3 band was detected at 38-43 kDa and 34 kDa in adult steers and calves. The IGFBP-3 antiserum used on the blots exhibited significant cross-reactivity with 34 kDa IGFBP-2. Furthermore, the 38-43 kDa IGFBP-3 bands were reduced to a 36 kDa band after deglycosylation, whereas the 34 kDa IGFBP-2 was intact. The plasma IGF-1, IGFBP-3 and other IGFBPs showed stability throughout a whole day. The change in live weight was found to be positively correlated to the plasma IGF-1 concentration (r = 0.6801, n = 64, p<0.05) and plasma IGFBP-3 (r = 0.6321, n = 64, p<0.05), while inversely correlated to plasma IGFBP-2 (r = -0.2919, n = 64, p<0.05). Furthermore, plasma IGF-1 was positively correlated to plasma IGFBP-3 (r = 0.6191, p<0.001), but was not correlated to plasma IGFBP-2. The portion of IGFBP-2 for total IGFBPs in calves was higher than in adult steers (p<0.05) and was decreased with growth, whereas that of IGFBP-3 was increased with increased live weight (p<0.05). The ratio IGFBP-3 for IGFBP-2 (BP-3/BP-2) was increased with growing of liveweight. Therefore, the changes in plasma IGF-1 level with increased liveweight may be related to the changes in plasma IGFBP-3 level and IGFBP-2 may give an important role in anabolic action of IGF-1 with the growth of body during calfhood in Holstein steers.

Evaluation of Serum Insulin-Like Growth Factor(IGF)-I, Insulin-Like Growth Factor Binding Protein(IGFBP)-2 and IGFBP-3 Levels in Healthy Korean Children (정상 어린이에서 혈청 인슐린양 성장인자-I과 인슐린양 성장인자 결합단백-2 및 -3의 농도 분석)

  • Yang, Gi Hoon;Jung, Hye Lim;Kim, Deok Soo;Shim, Jae Won;Shim, Jung Yeon;Park, Moon Soo
    • Clinical and Experimental Pediatrics
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    • v.48 no.3
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    • pp.298-305
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    • 2005
  • Purpose : We performed this study to evaluate the mean serum levels of insulin-like growth factor (IGF)-I, insulin-like growth factor binding protein(IGFBP)-2 and IGFBP-3 in healthy Korean children according to age and sex. Methods : Ninety two healthy children, consisting of 42 boys and 50 girls, were classified into five groups according to age : neonate; infancy; early childhood; late childhood; and adolescence. We measured serum levels of IGF-I, IGFBP-2 and IGFBP-3 by enzyme-linked immunosorbent assay(ELISA) and analysed the serum levels according to sex and age group. Results : For boys, the mean serum levels of IGF-I(ng/mL) in neonate, infancy, early childhood, late childhood and adolescence were $41.1{\pm}3.6$, $70.9{\pm}33.7$, $103.5{\pm}97.2$, $89.8{\pm}46.5$ and $51.4{\pm}27.8$, respectively. Those of IGFBP-2(ng/mL) were $8.2{\pm}3.4$, $5.8{\pm}0.4$, $9.3{\pm}4.0$, $9.5{\pm}1.1$ and $7.0{\pm}0.5$, respectively. Those of IGFBP-3(ng/mL) were $559.2{\pm}215.2$, $1,333.3{\pm}692.5$, $2,254.6{\pm}1,513.8$, $2,447.1{\pm}1,464.2$, $1,533.6{\pm}807.4$, respectively. For girls, the mean serum levels of IGF-I(ng/mL) according to five age groups were $53.3{\pm}9.5$, $99.3{\pm}45.8$, $69.6{\pm}51.1$, $106.2{\pm}67.0$ and $145.1{\pm}127.8$, respectively. Those of IGFBP-2 (ng/mL) were $9.1{\pm}7.4$, $5.3{\pm}0.9$, $6.9{\pm}2.0$, $10.5{\pm}3.0$ and $7.9{\pm}1.3$, respectively. Those of IGFBP-3(ng/mL) were $858.2{\pm}433.4$, $1,834.8{\pm}851.3$, $1,404.3{\pm}570.2$, $2,203.5{\pm}899.4$ and $2,029.3{\pm}1,316.7$, respectively. There were significant positive correlations observed between IGF-I and IGFBP-3 levels(r=0.589, P=0.000). Conclusion : IGF-I and IGFBP-3 levels increased as children get older. The peak level of IGFBP-3 was observed in late childhood for both boys and girls, suggesting a current trend of children reaching peak growth velocity before adolescence. The IGFBP-2 level was higher in neonates compare to infancy, suggesting that IGFBP-2 is an important substance for fetal growth.

Enhancement of Growth Performance in Transgenic Rabbits with Overexpressing Growth Hormone Receptor and IGF-1 Receptor Genes

  • Chang, Suk-Min;Kim, Hyun-Ju;Kim, Jin-Young;Park, Wha-Sik;Im, Kyung-Soon;Dong IL Jin
    • Proceedings of the KSAR Conference
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    • 2002.06a
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    • pp.95-95
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    • 2002
  • Transgenic rabbits were produced by micoinjection of DNA containing metallothionein promoter ligated to growth hormone receptor (GHR) and IGF-l receptor (IGF-lR) genes. Founder transgenic rabbits transmitted transgenes into pups with Medelian ratio. The mRNA expression of transgenes using Northern blotting with probes of IGF-IR and GHR genes was checked in liver of transgenic rabbits. Transgenic rabbits with IGF-IR and GHR genes more expressed mRNA than control non-transgneic rabbits. (omitted)

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Expression Characteristics of Proteins of the Insulin-like Growth Factor Axis in Non-small Cell Lung Cancer Patients with Preexisting Type 2 Diabetes Mellitus

  • Ding, Jing;Tang, Jie;Chen, Xin;Men, Hai-Tao;Luo, Wu-Xia;Du, Yang;Ge, Jun;Li, Cong;Chen, Ye;Cheng, Ke;Qiu, Meng;Liu, Ji-Yan
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.5675-5680
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    • 2013
  • Background: Preexisting type 2 diabetes mellitus (T2DM) affects the prognosis and mortality of patients with some cancers. Insulin like growth factor (IGF) and insulin receptor (IR) signaling axes play important roles in both cancer and diabetes development. We aimed to explore the expression characteristics of proteins in IGF/IR axis in non-small cell lung cancer (NSCLC) cases with preexisting T2DM. Methods: Fifty-five NSCLC patients with preexisting T2DM were retrospectively included and matched by 55 NSCLC without diabetes at a 1:1 ratio. The expression of proteins in IGF/IR axis was detected by immunohistochemical staining. Clinicopathological data were collected to analyze their relationship with the protein expression. Results: Both IGF 1 receptor (IGF-1R) and insulin receptor substrate 2 (IRS-2) showed higher expression in the NSCLC with T2DM group, compared with those without T2DM. The high expression of IGF-1R and IRS-2 were found to be negatively associated with lymph node metastases and T staging in the T2DM group, respectively, and IRS-2 expression was also found more in the subgroup whose T2DM duration was more than 4 years. No difference was detected in the expression of IRS-1, IGF-1, IGF-2, IGFBP3, IR and mTOR between groups with or without T2DM. Conclusion: Our study found higher expression of IGF-1R and IRS-2 proteins in NSCLC patients with preexisting T2DM, and that there was an association with early stage NSCLC, which suggested that IGF signaling may play an important early event in development of NSCLC associated with diabetes.

Effect of rGH on Body Growth and Udder Development on Korean Native Heifers (외인성 성장호르몬이 한우의 성장 및 유방의 발달에 미치는 영향)

  • 최광수;신원집;최호성
    • Korean Journal of Animal Reproduction
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    • v.22 no.1
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    • pp.81-87
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    • 1998
  • This experiment was carried out with 12 Korean native heifers(8~12month old, body weight, 160~240kg) raised at a farm of Chang-Soo Livestock Cooperatives to evaluate the effects of rGH(recombinant growth hormone) on serum concentrations of growth hormone, estrogen, and IGF-I, weight gain, teat volume gain and processing enzyme activity of IGF-I, binding protein III at 28 day intervals. Animals used were injected with 250mg rGH at 14 day intervals from December to Ferbruary in 1994. The significant difference was found in the group of treatment on the 4th week in the endogenous GH(p<.01) and 8th week in estrogen and IGF-I(p<.05) after injectin of rGH in Korean native heifers. There were significant differences between control group and treatment group in weight and teat volume on 8th week after treatment(p<.05). Processing enzyme activity before injection of rGH were low. However, heifers injected with 250mg of rGH showed that processing enzyme activity of IGF binding protein was highly increased throughout the experiment. Present results suggest that injection of exogenous rGH to heifers can increase the growth performance and udder development of Korean native heifers by the endogenous hormonal changes.

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Correlation of Cord Serum Adiponectin and IGF-I with Fetal Growth in Healthy Term Neonates (제대혈 Adiponectin과 IGF-I이 태아성장에 미치는 영향)

  • Kim, Ji-Young;Cho, Su-Jin;Kim, Hae-Soon;Park, Hye-Sook;Park, Eun-Ae
    • Neonatal Medicine
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    • v.15 no.1
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    • pp.38-43
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    • 2008
  • Purpose : The purpose of this study was to evaluate the relationship between cord serum adiponectin (APN) and IGF-I concentrations and fetal growth. Methods : Umbilical cord serum APN and IGF-I concentrations were measured in healthy term singleton deliveries (n=72). The association of cord serum APN and IGF-I concentrations was evaluated in relation to birth weight, height, head circumference, gender, ponderal index, placental weight, feto-placental (F/P) weight ratio, maternal weight gain, and maternal body mass index (BMI). Results : The mean cord serum APN was 29.2${\pm}$10.46 $\mu$g/mL. The cord serum APN and birth weight demonstrated a bell-shape relationship. The cord serum APN concentration was higher in females than males (P=0.001). The cord serum APN was negatively correlated with maternal BMI (r=-0.301, P=0.027), but the mean cord serum APN concentration was not correlated with birth height, birth head circumference, ponderal index, placental weight, F/P ratio, or maternal weight gain. The mean cord serum concentrations of IGF-I was 51.26${\pm}$21.54 ng/mL. The cord serum IGF-I concentration was positively correlated with birth weight (r=0.312, P=0.009), but not birth height, ponderal index, placental weight, F/P weight ratio, or maternal BMI. Conclusion : APN demonstrated a bell-shaped relationship with birth weight in healthy term infants. IGF-I was highly correlated with fetal growth, especially birth weight.

Analysis of cytosine adenine(CA) repeat polymorphism of the IGF-I gene and influence on serum IGF-I levels in healthy children and adolescents (한국인 소아 및 청소년에서 IGF-I 유전자형의 분석과 cytosine-adenine(CA) repeat 유전자 다형성이 혈중 IGF-I 농도에 미치는 영향)

  • Ko, Myung Jin;Hwang, Tae Gyu;Lee, Jeong Nye;Chung, Woo Yeong
    • Clinical and Experimental Pediatrics
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    • v.49 no.12
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    • pp.1340-1347
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    • 2006
  • Purpose : The aim of the present study was to investigate the role of polymorphic cytosine adenine (CA) repeat of the IGF-I gene in the age-related alterations of serum IGF-I levels in healthy children. Methods : Two hundred and forty three normal healthy children (136 boys; 107 girls) aged between 7 and 15 years were enrolled in the present study. The primers were designed to cover the promoter regions containing the polymorphic CA repeat. Data were analyzed using GeneMapper software, version 3.7. All analyses were performed using MEDCALC software packages. Results: Deletion of 2 bp (G, A) following 3' of CA repeat were observed in all Korean children. The CA repeat sequences ranged from 17 to 23, and 19 CA repeat were the most common with an alleles frequency of 39.3 percent. Considering genotypes, 63.8 percent of subjects were homozygote or heterozygote for 19 CA repeat (192 bp allele), suggesting that this is wild type allele from which all other alleles originated in Korean children. Homozygote for 19 CA repeat were 14.7 percent, heterozygote for 19 CA repeat was 49.1 percent and 19 CA noncarriers totalled 36.2 percent. In 19 CA repeat noncarriers, the mean height, weight and serum IGF-I level were lower compared with those of 19 CA homozygous carriers, but statistically not significant. Correlations between serum IGF-I level and age according to the IGF-I genotypes revealed statistically significant relationships in the all groups, in the 19 CA repeat carrier group and, even in the noncarrier group. Conclusions : There were no significant differences of the mean height, weight and serum IGF-I levels among three different genotype groups. Also, there were no significantly different correlations between 19 CA repeat polymorphisms and serum IGF-I levels, according to genotype. Our results suggest that the IGF-I 19 CA repeat gene polymorphism is not associated with circulating IGF-I levels in healthy children.